MOLMAKER - DE-NOVO GENERATION OF 3D DATABASES FOR USE IN DRUG DESIGN

A program, MOLMAKER, is described which, in conjunction with a 2D-3D c onversion program and 3D database software, can generate de novo 3D da tabases to aid in drug design. MOLMAKER is based upon graph-theoretica l techniques for vertex degree set generation and constructive enumera tion of molecular graphs. The generated molecular graphs are then func tionalised in a probabilistic manner but in accordance with various co nstraints specified by the user. The resulting connection tables can b e converted into 3D structures by commercial software and loaded into a 3D database for pharmacophore searching. The utility of MOLMAKER is illustrated by two examples of interest from the recent scientific lit erature: the design of novel protein kinase C agonists and of a bridgi ng ligand for cyclophilin-calcineurin.